Elongated Particles Show a Preferential Uptake in Invasive Cancer Cells.

IF 4.4 3区 材料科学 Q2 CHEMISTRY, MULTIDISCIPLINARY Nanomaterials Pub Date : 2024-11-25 DOI:10.3390/nano14231891
Talya Cohen, Chalom Zemmour, Ora T Cohen, Ofra Benny
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Abstract

Mechanically driven cellular preference for drug carriers can enhance selectivity in cancer therapy, underscoring the importance of understanding the physical aspects of particle uptake. In this study, it was hypothesized that elongated particles might be preferentially taken up by deformable, aggressive cancer cells compared to normal cells. Two film-stretching methods were tested for 0.8-2.4 μm polystyrene (PS) particles: one based on solubility in organic solvents and the other on heat-induced softening. The heat-induced method produced more homogenous particle batches, with a standard deviation in the particle aspect ratio of 0.42 compared to 0.91 in the solvent-based method. The ability of cells to engulf elongated PS particles versus spherical particles was assessed in two subsets of human melanoma A375 cells. In the more aggressive cancer cell subset (A375+), uptake of elongated PS particles increased by 10% compared to spherical particles. In contrast, the less aggressive subset (A375-) showed a 25% decrease in uptake of elongated particles. This resulted in an uptake ratio between A375+ and A375- that was 1.5 times higher for elongated PS particles than for spherical ones. To further demonstrate relevance to drug delivery, elongated paclitaxel-loaded biodegradable, slow-releasing poly(lactic-co-glycolic) acid (PLGA) particles were synthesized. No significant difference in cytotoxic effect was observed between A375+ and A375- cells treated with spherical drug-loaded particles. However, treatment with ellipsoidal particles led to a significantly enhanced cytotoxic effect in aggressive cells compared to less aggressive cells. These findings present promising directions for tailored cancer drug delivery and demonstrate the importance of particle physical properties in cellular uptake and drug delivery mechanisms.

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细胞对药物载体的机械偏好可提高癌症治疗的选择性,这就强调了了解颗粒摄取的物理方面的重要性。本研究假设,与正常细胞相比,可变形的侵袭性癌细胞可能会优先摄取细长颗粒。针对 0.8-2.4 μm 聚苯乙烯(PS)颗粒测试了两种薄膜拉伸方法:一种基于有机溶剂中的溶解度,另一种基于热诱导软化。热诱导法产生的颗粒批次更均匀,颗粒长宽比的标准偏差为 0.42,而溶剂法的标准偏差为 0.91。在人类黑色素瘤 A375 细胞的两个亚群中评估了细胞吞噬拉长 PS 粒子和球形粒子的能力。在侵袭性较强的癌细胞亚群(A375+)中,细长 PS 粒子的吸收比球形粒子增加了 10%。相比之下,侵袭性较低的亚群(A375-)对细长颗粒的吸收减少了 25%。这导致 A375+ 和 A375- 对细长 PS 粒子的吸收比是球形粒子的 1.5 倍。为了进一步证明药物递送的相关性,我们合成了可生物降解、缓释的拉长型紫杉醇负载聚乳酸-共聚乙醇酸(PLGA)颗粒。用球形载药颗粒处理 A375+ 细胞和 A375- 细胞,细胞毒性效果无明显差异。然而,与侵袭性较低的细胞相比,用椭圆形颗粒处理侵袭性细胞可显著增强细胞毒性效果。这些发现为量身定制的抗癌药物递送指明了方向,并证明了颗粒物理特性在细胞吸收和药物递送机制中的重要性。
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来源期刊
Nanomaterials
Nanomaterials NANOSCIENCE & NANOTECHNOLOGY-MATERIALS SCIENCE, MULTIDISCIPLINARY
CiteScore
8.50
自引率
9.40%
发文量
3841
审稿时长
14.22 days
期刊介绍: Nanomaterials (ISSN 2076-4991) is an international and interdisciplinary scholarly open access journal. It publishes reviews, regular research papers, communications, and short notes that are relevant to any field of study that involves nanomaterials, with respect to their science and application. Thus, theoretical and experimental articles will be accepted, along with articles that deal with the synthesis and use of nanomaterials. Articles that synthesize information from multiple fields, and which place discoveries within a broader context, will be preferred. There is no restriction on the length of the papers. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible. Full experimental or methodical details, or both, must be provided for research articles. Computed data or files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material. Nanomaterials is dedicated to a high scientific standard. All manuscripts undergo a rigorous reviewing process and decisions are based on the recommendations of independent reviewers.
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